The isoenzyme family of protein kinase C (PKC) plays a key role in signal transduction and cellular regulation (Y. Nishizuka, 1988). From the observation that the tumor promoting phorbol esters are able to stimulate PKC activity (Y. Nishizuka, 1984), it was concluded that inhibitors of this enzyme could be useful for cancer chemotherapy. PKC inhibitors have been extensively investigated as potential drugs for the treatment of cancer. Accordingly, a goal of the present invention is to provide new antitumor agents; these compounds are alkaloids with significant activity against several cancer cell lines.
Yet another objective of this invention is to provide pharmaceutical compositions for administering to a patient in need of treatment using the active compounds described herein.
Microbial products are interesting because their industrial production is well established at present times. Therefore, another objective of this invention is directed to the production of the active compounds and to their isolation and purification from the resulting fermentation broth.